{"doi":"10.1242/dev.202686","title":"In preprints: tick, tick, somite – an intrinsic timer regulates segmentation","abstract":"Our vertebrae and peripheral nerves are periodically arranged along the body axis, representing a fundamental feature of our body plan – segmentation. This feature is first established in the early embryo by the formation of repeated epithelial blocks called somites on either side of the neural tube. The process of somite formation is fascinating because it occurs sequentially from head to tail in coordination with body axis elongation. Each somite periodically buds off from the anterior-most part of the unsegmented tissue termed presomitic mesoderm (PSM). This process is precisely orchestrated by an oscillating gene regulatory network famously known as the segmentation clock, which is conserved from fish to humans. In each cycle of somite formation, activity of the clock is initiated in the posterior PSM and travels anteriorly as a kinematic wave. It has long been observed that the traveling wave progressively slows down along the PSM. That is, the oscillation period in the anterior PSM is longer than that of the posterior PSM. This dynamic feature has been proposed to regulate somite morphogenesis and patterning (Lauschke et al., 2013; Shih et al., 2015; Sonnen et al., 2018), yet the mechanisms underlying the slowing oscillations along the PSM remain unclear. In Rohde et al. (2023 preprint), the authors combined in vitro and in vivo quantifications to provide new insights. Their elegant work suggests that the slowing of clock oscillations is a cell-autonomous property. By concurrently analyzing cell differentiation, they further proposed a model of segmentation governed by an intrinsic timer that can be tuned by extrinsic factors.A series of in vitro studies have revealed that the clock oscillation itself is autonomous and does not require extrinsic factors such as cell-cell contact (Diaz-Cuadros et al., 2020; Hubaud et al., 2017; Webb et al., 2016; Yoshioka-Kobayashi et al., 2020). In this preprint, the authors went a step further to demonstrate that the temporal evolution of the oscillation profile, which underlies the wave slowing on the tissue scale, is also cell intrinsic (Rohde et al., 2023 preprint). They dissociated the posterior PSM of zebrafish embryos and cultured isolated cells in the absence of signaling molecules. By following the expression of a fluorescently tagged clock component, Her1, they observed that clock oscillations autonomously slow down before abruptly arresting. When single cells in the embryo from the same PSM region were analyzed, similar key features of progressive period slowing were found. This remarkable mirroring between in vitro and in vivo suggests that oscillation slowing is cell autonomous independent of tissue environment. As many models explaining wave slowing focus on extrinsic regulation such as coupling delay between cells (Takagi et al., 2020), this finding brings new perspectives for understanding the spatial dynamics of oscillations along the PSM.In concert with oscillation arrest, the onset of a segmental differentiation marker Mesp-ba was detected in isolated single cells, consistent with tissue-level expression patterns in the embryo. Overall, more noise regarding oscillation dynamics, such as cycle number and amplitude, as well as the coordination between clock arrest and Mesp-ba expression, was observed among cells in vitro, suggesting that extrinsic factors normally present in the embryo might tune the precision of oscillations and differentiation. Consistent with previous findings (Diaz-Cuadros et al., 2020; Miao et al., 2023), the Mesp-ba onset is independent of clock dynamics because similar patterns of expression were observed in isolated cells lacking a functional clock. Nevertheless, the temporal association between clock dynamics and Mesp-ba onset was maintained in the presence of exogenous FGF8, which prolonged the duration of oscillations in vitro and accordingly delayed the onset of differentiation. Altogether, these suggest that a cell intrinsic timer governs bo","journal":"Development","year":2024,"id":493803,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":700829,"name":"Yuchuan Miao","orcid":"0000-0003-0600-6609","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-19T02:09:03.883685Z","pmid":"38293868","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}